Incidence trends for invasive and non-invasive disease are explored. A nested case control study of those women who progress from non-invasive disease to carcinoma is performed. The incidence of vulval carcinoma in Grampian remains stable. Incidence rates of all non-invasive chronic vulval skin disorders, regardless of underlying aetiology are rising dramatically. Age specific incidence rates suggest that there may be significant ascertainment bias in rising incidence rates for each of these skin disorders. No distinction could be found between the relative risks for women with vulval litchen sclerosus or vulval intraepithelial neoplasia developing subsequent carcinoma. Vulval squamous hyperplasia appears to be of low malignant potential. The malignant risk of vulval lichen sclerosus or vulval intraepithelial neoplasia within Grampian is currently in the order of 9% over ten years of follow-up. The presence of HPV 16 DNA does not appear to confer an increased risk of subsequent malignant transformation in women with biopsy-proven chronic vulval skin disorders. Although p-53 overexpression is not associated with an increased risk of subsequent malignant transformation, there are patterns of altered expression that may identify a high risk group of women. Those women that have been identified as suffering from a chronic vulval skin disorder before they develop invasive disease appear to have more favourable prognostic factors at presentation. The primary role of viral carcinogenesis in vulval carcinoma has been overestimated in the current literature. p53 aberrations may be a unifying factors in the biology of vulval carcinoma, with HPV acting as a co-factor in some cases. Aggressive surgical management for vulval intraepithelial neoplasia solely for the purposes of anticipating a rise in invasive disease rates should be resisted. An increase in resource allocation for the purpose of close surveillance of women with vulval lichen sclerosis or vulval intraepithelial neoplasia now seems justified.

No description available.

Following a review of methods for measuring the optical properties of tissue, the majority of this thesis is concerned with the design, construction, calibration and use of a solid, tissue equivalent phantom. The phantom material is a clear polyester plastic. This is obtained in unpolymerised form, scattering particles and absorbing dyes are added to it, and it is then polymerised to form a stable solid. Purely scattering and absorbing phantoms were made separately, and their optical properties were measured using a specially built system. This has a co-linear collimated light source and detector, and measures the unscattered light transmitted through a sample as a function of its thickness. Other methods of measuring the optical coefficients of tissue were tested with this phantom. One of these uses integrating spheres to measure the transmitted and reflected light from a sample. A model of light transport (in this case a Monte Carlo model) is used to convert these measurements into scattering and absorption coefficients. It was found that the measurement of scattering coefficient was reasonably accurate, but that the absorption coefficient was overestimated at the low values typical of tissue. A measurement of the optical properties of bone was made with this system. The other system investigated uses the diffusion theory to calculate optical properties from measurements made through a thick slab. The material was also employed to create a test phantom for near infrared spectroscopy machines. This provides a diffusing medium with an attenuation that is variable in discrete steps over three orders of magnitude. The relative attenuation between steps is totally wavelength independent. This phantom was adopted by the EC concerted action on near infrared spectroscopy and imaging. Finally, the phantom was used to create test objects with which to investigate the potential of imaging with infrared light.

No description available.

xiv, 241, lix leaves : tables, graphs ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology, 1977

No description available.

CD40 is an important antigen involved in immune regulation and anti-CD40 antibody therapies against human CD40 expressing tumours may be particularly advantageous. The antibody could induce tumour response in two ways. Firstly it might have a direct anti-tumour effect and secondly it could 'boost' the immune system to provide a heightened immune response that evades tumour tolerance. This project has explored the effects of CD40 ligation of a variety of CD40 expressing tumours including transformed human B cell lines (RL and Daudi), human epithelial cell lines (MG79 [ovarian] and Caski [cervical]) and primary human B cell non-Hodgkin's lymphomas obtained, with consent, from patients undergoing excision lymph node biopsy or splenectomy. The ligation of CD40, on transformed human B cell lines, using chinese hamster ovary cells transfected to express human CD40L and human soluble CD40L has shown significant cellular growth inhibition (p<O.001). Ligation of CD40 on human epithelial cell lines using human soluble CD40L has also resulted in significant growth inhibition. In primary B cell human non-Hodgkin's lymphomas ligation of CD40 with both CD40L expressing CHO cells and human soluble CD40L in the presence of human IL4 has caused significant cellular proliferation (p<O.001) and induced upregulation of cell surface and costimulatory molecules including CD80, CD86, CD58, CD54. Anti-tumour activity has been identified in a xenograft model of a transformed human B cell line (Daudi) treated with both a mouse anti-human CD40 antibody and a chimeric human anti-CD40 antibody. I have performed important preclinical toxicology studies testing mouse anti -CD40 (3/23) by injecting the antibody intraperitoneally or intravenously in to BALB/c mice. The mice have been culled following treatment and a reversible dose dependent transaminitis associated with microscopic evidence of a reversible Iympho-granulomatous hepatitis, that at the highest dose levels is acutely necrotising, has been identified. These antiCD40 antibody toxicology studies are essential before a protocol for a phase I trial of human anti-CD40 antibody against CD40 expressing human tumours is developed. I have developed a new chimeric human anti -CD40 antibody containing human constant regions and mouse variable regions. This antibody is currently undergoing large scale production for a proposed trial to treat patients with CD40 expressing tumours (excluding low-grade non-Hodgkin's lymphoma) who have failed conventional therapies.

Brain tumours are the second most common malignancy in children(1) (2), and despite some advancements being made over the last 2 decades, patient outcomes in general remain poor when compared with other childhood cancers. Optimal treatment of children with brain tumours is challenging and expertise and resources are not widely available in South Africa. This is important because the outcomes of children with brain tumours depend critically on the expertise and resources of a multidisciplinary team tasked with their treatment. Despite the importance of paediatric brain tumours though, little is known about childhood brain tumours in South Africa as limited data have been published and there have been no funded studies to support research in this area. In addition, we know very little about the resources available across the country to treat these children. In international centres of excellence the best outcomes are achieved by combining good epidemiological data, strong multidisciplinary teams, centralization or regionalization of services, available resources, and a research foundation. To start, we need to know more about the patients presenting to us with brain tumours. PURPOSE The overall aim of this project was to collect epidemiological data for childhood brain tumours at a tertiary paediatric hospital in South Africa with a dedicated multidisciplinary team. METHODS Study design: A retrospective review of records of patients diagnosed with a primary brain tumour and who presented to Red Cross Children’s Hospital (RCCH) system from 1 January 1996 to 31 December 2017. 2 Patient selection &amp; data collection: Patients were identified by combining databases and admission logs from paediatric neurosurgery, oncology, radiotherapy, histopathology and radiology. Data collected included: age at diagnosis, sex, province of referral, tumour site and diagnosis. RESULTS A total of 554 paediatric patients with primary brain tumours were identified over the study period. Tumours were more common among males (55.4%) and were located in the supratentorial compartment in 52%. The median age at diagnosis was 5.92 years. The commonest tumours were astrocytomas (n=114 patients; 20.3%), followed by medulloblastomas (incl. PNETs) (n=107 patients; 19.1%), and craniopharyngiomas (n=55; 9.8%). As expected, most patients referred and seen at RCCH/GSH were from the expected drainage area in the Western Cape (73%), but a significant number of referrals (27%) were from outside the province referrals, especially in the last 10 years. CONCLUSION Our findings were largely consistent with the published literature in terms of histological diagnosis, sex profile and age ranges for children diagnosed with brain tumours with some small differences possibly related to referral bias. More patients than expected were referred from outside of the province, which emphasizes the need for establishing an ongoing tumour database registry and co-ordinating patient care across institutions. A follow-up study to assess patient management and outcomes is of critical importance to assess resource availability and patient outcomes.

MMed, Otorhinolaryngology, Faculty of Health Sciences, University of the Witwatersrand / This study is a six year retrospective review of the histopathology of nasopharyngeal masses in adult patients who underwent a biopsy in theatre at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) from 1st January 2003 to 31st December 2008. Eighty one patients were included in this study. They comprised of 54 males (67%) and 27 females (33%) aged between 18 and 82 years. There was no statistical difference between the two genders in terms of their ages (p= 0.39). Fifty two patients (64%) had benign disease and 29 patients (36%) had malignant disease (ratio 1.8:1). Thirty four males (65%) and 18 females (35%) had benign disease. Twenty males and 9 females had malignant disease. There was no significant correlation between gender and malignancy (r= -0.04, p=0.75). The independent predictors of the nature of the tumour were: nasal congestion, epistaxis, hearing loss, otalgia and Human Immunodeficiency Virus (HIV) status. The statistically significant positive predictors of malignancy were the presence of nasal congestion, epistaxis and otalgia. The presence of at least one or more of these symptoms was associated with an odds ratio of 3.06 for malignant disease. (CI= 1.17-8.01). The presence of hearing loss was independently associated with benign disease (p=0.031). The HIV status was known in 41 of the 81 patients. Of the 41 patients whose HIV status was known, 25 were male and 16 were female. The HIV positive patients comprised of 19 males (76% of all males) and 9 females (56% of all females). The presence of HIV infection was independently associated with benign disease. The absence of HIV infection was in fact associated with malignant disease, with an odds ratio of 4.00 and 95% confidence intervals of 1.04 to 15.43.

In light of the increasing interest in the syntheses of fluorocarbohydrates as well as in their radiolabelled analogues for use in positron emission tomography (PET), a two- step synthesis of 2-fluoro-2-deoxy-ß-D-allose (2-FDpA) has been developed. The present synthesis employed electrophilic fluorination of 3,4,6-tri-O-acetyl-D-glucal in anhydrous HF (aHF) solvent using F2 and AcOF and was more rapid and efficient than the existing synthesis of 2-deoxy-2-fluoro-D-allose, with a total synthesis time of approximately 45 min, and less laborious. The synthesis proved to be higly regio- and Stereosective, which is often hard to achieve from electrophilic fluorinations. The synthetic route to 2-FDßA was used to obtain the 18F-Iabelled analogue, 2-[18F]FDßA, for the first time with the anticipation that the labelled compound will be of use as a diagnostic agent for the detection and assessment of different tumours as well as for monitoring D-allose metabolism. The overall decay-corrected radiochemical yields (RCY) of the products resulting from radiofluorination of TAG in aHF with [18F]F2 and [18F]AcOF were 33 ±3% and 9 ±2%, respectively, with respect to [18FJF2. The RCY of 33 ±3% is the highest reported for direct fluorinations of TAG using [18FJF2 in any solvent. The radiochemical purities of 2-[18F]FDßA were 96 ±3% and 91 ±8% as determined by radio-HPLC and radio-TLC, respectively. Preliminary in vivo studies using normal rats showed significant differences between the uptake of 2-[18F]FDßA and 2-[18F]FDG, the most commonly used PET radiotracer for detection of various types of cancers. In addition, an animal study with a Polynoma Middle T mouse showed retention of 2-[18F]FDßA in the tumour. The 18F-Iabelling technique was also used as a mechanistic probe for the synthesis of 2-FDßA in the present study. / Thesis / Master of Science (MSc)